Anatomy of noise in quantitative biological Raman spectroscopy

Abstract

Raman spectroscopy is a fundamental form of molecular spectroscopy that is widely used to investigate structures and properties of molecules using their vibrational transitions. It relies on inelastic scattering of monochromatic laser light irradiating the specimen. After appropriate filtering the scattered light is dispersed onto a detector to determine the shift from the excitation wavelength, which appears in the form of characteristic spectral patterns. The technique can investigate biological samples and provide real-time diagnosis of diseases. However, despite its intrinsic advantages of specificity and minimal perturbation, the Raman scattered light is typically very weak and limits applications of Raman spectroscopy due to measurement (im)precision, driven by inherent noise in the acquired spectra. In this article, we review the principal noise sources that impact quantitative biological Raman spectroscopy. Further, we discuss how such noise effects can be reduced by innovative changes in the constructed Raman system and appropriate signal processing methods.